Phosphatidylglycerol Supplementation Alters Mitochondrial Morphology and Cardiolipin Composition

The pathogenic variant of the <i>TAZ</i> gene is directly associated with Barth syndrome. Because tafazzin in the mitochondria is responsible for cardiolipin (CL) remodeling, all molecules related to the metabolism of CL can affect or be affected by <i>TAZ</i> mutation. In this study, we intend to recover the distortion of the mitochondrial lipid composition, especially CL, for Barth syndrome treatment. The genetically edited <i>TAZ</i> knockout HAP1 cells were demonstrated to be a suitable cellular model, where CL desaturation occurred and monolyso-CL (MLCL) was accumulated. From the species analysis by mass spectrometry, phosphatidylethanolamine showed changed species content after <i>TAZ</i> knockout. <i>TAZ</i> knockout also caused genetic down-regulation of <i>PGS</i> gene and up-regulation of <i>PNPLA8</i> gene, which may decrease the biosynthesis of CLs and increase the hydrolysis product MLCL. Supplemented phosphatidylglycerol(18:1)₂ (PG(18:1)₂) was successfully biosynthesized to mature symmetrical CL and drastically decrease the concentration of MLCL to recover the morphology of mitochondria and the cristae shape of inner mitochondria. Newly synthesized mature CL may induce the down-regulation of <i>PLA2G6</i> and <i>PNPLA8</i> genes to potentially decrease MLCL production. The excess supplemented PG was further metabolized into phosphatidylcholine and phosphatidylethanolamine.